Legg-Calve-Perthes Disease Patients Research Articles

Thrombomodulin and GFC levels in Legg–Calve–Perthes disease

Legg–Calve–Perthes disease (LCPD) is a self-limited microvascular disorder leading to the occlusion of the femoral blood supply, which results in bone necrosis. Endothelial injury and hemostatic alterations may play a role in the microvascular compromise and decreased blood flow, which occur during the course of LCPD. Global fibrinolytic capacity (GFC) is a novel assay reflecting the overall fibrinolysis response resulting from the dynamic interactions of numerous stimulatory and inhibitory fibrinolytic molecules. Circulating soluble thrombomodulin (TM) reflects endothelial activation and/or injury. It is a cofactor in the clinically important protein C natural anticoagulant system. Beyond the coagulation pathway it is shown to have effects on biological events, especially inflammation. The aim of this study was to determine GFC and TM levels in LCPD patients. The study included 77 children in two groups. Group I consisted of 42 patients with LCPD and Group II (control) comprised 35 healthy children. Median (interquartile ratios) GFC and TM levels were significantly higher in the LCPD patients (Group I) (p<0·0001 and p=0·049, respectively). Circulating high levels of soluble TM may be associated with ongoing endothelial injury or ongoing inflammation during the disease course. Along with increased overall fibrinolytic response, increased TM may be a compensatory reaction to thrombosis. Further investigations are needed to elucidate the endothelial, anticoagulant, and fibrinolytic kinetics associated with the microvascular compromise and self-limiting nature of LCPD.

Hip Arthrography Under General Anesthesia to Refine the Definition of Hinge Abduction in Legg-Calvé-Perthes Disease

Hinge abduction is widely accepted as a poor prognostic factor in Legg-Calvé-Perthes disease (LCPD), whereas the exact definition of hinge abduction remains ill defined. The purpose of this diagnostic study was to refine the definition of hinge abduction in LCPD using conventional hip arthrography under general anesthesia. Among 350 hips in 332 LCPD patients, we reviewed 92 hips in 90 patients (75 boys and 15 girls) who consecutively underwent arthrography under general anesthesia because of an expected poor prognosis. The mean age at LCPD onset was 8.2 years (range, 4-13 years). With respect to lateral pillar classification, 25 hips were classified as group B, 27 as B/C border, and 40 as C. Subluxation (>or=3-mm difference from unaffected side) was present in 81 (88%) of the 92 hips. The modified Waldenström classification was used for evaluating the radiographic stage of disease at the time of arthrography: 80 hips were classified as fragmentation stage and 12 as reossification stage. Hinge abduction was defined as an increased subluxation index in maximum abduction and/or a positive impingement sign. Under this definition, 11% (10 hips) of the study group had hinge abduction. The range of abduction under general anesthesia (40 degrees) was significantly greater than in the awake condition (24 degrees, P < 0.0001). The subluxation index and the impingement sign proved to be reliable indicators for diagnosing hinge abduction. Conventional arthrography remains useful. General anesthesia provided an analgesic effect and muscle relaxation. Level II (diagnostic study, development of diagnostic criteria on the basis of consecutive patients).

A Histological and Ultrastructural Study of the Iliac Crest Apophysis in Legg-Calve-Perthes Disease

Legg-Calve-Perthes disease (LCPD) is a common hip disorder in children characterized by avascular necrosis of the proximal capital femoral epiphysis. The underlying etiology of the vascular disturbance is still unknown, but it is suggested that LCPD may be a part of a generalized constitutional disorder associated with growth disturbance of bone and cartilage tissue. In this study, the biopsy specimens of the iliac crest apophysis from LCPD patients were examined histologically and ultrastructurally to determine preexisting generalized abnormalities of endochondral ossification. Iliac crest apophysis cartilage was taken during Salter innominate osteotomy from 11 children (8 boys and 3 girls) with LCPD at an average age of 7.8 years. As controls, the samples were also obtained from 10 children (2 boys and 8 girls) at an average age of 6.3 years undergoing Salter osteotomy due to residual acetabular dysplasia after reduction of developmental dysplasia of the hip. Each iliac crest apophysis specimen was examined histologically (Toluidine blue staining and Sudan III staining) and ultrastructurally. Although there were no obvious differences in Toluidine blue-stained sections of the iliac crest cartilage between LCPD and control patients, the Sudan III-positive chondrocytes in the resting cartilage were more prominent in the LCPD specimens than in the control specimens. These sudanophilic granules were confirmed to be lipid droplets by electron microscopic examinations. Ultrastructural examinations of the resting chondrocytes from 3 LCPD patients demonstrated numerous cytoplasmic inclusion bodies with electron dense materials, which were similar to those seen in some of the mucopolysaccharidoses. Increased lipid droplets and numerous cytoplasmic inclusions filled with fibrillar materials were suggestive of the initial metabolic changes of the chondrocytes, which may have a pivotal role in degenerating matrix and lead to vulnerability of the cartilage tissue. Our results indicated that generalized insufficiency in growth cartilage metabolism may be related to the onset of the disease in some LCPD patients.

A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family

Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity. Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases.

Pathoanatomical Factors Responsible for Femoral Shortening in Legg-Calve-Perthes Disease

Purpose: The purpose of this study was to determine the relative contributions made by pathoanatomical factors responsible for femoral shortening in Legg-Calve-Perthes disease (LCPD), and to devise a method of reducing the amount of residual shortening based on a better understanding of its pathoanatomy and developmental pattern in LCPD. Materials and Methods: We measured shortening of three anatomical components, namely, the femoral epiphysis, neck, and diaphysis on the teleoroentgenograms of 106 LCPD patients, comprised of 35 children with active disease, 24 in the healing stage, and 47 at skeletal maturity. Results: The proportional contributions made by these 3 anatomical components to residual shortening at skeletal maturity were; 20% by the epiphysis (epiphyseal flattening), 53% by the neck (physeal growth retardation), and 27% by the diaphysis (underuse atrophy). These contributions differed according to disease stage and shortening severity. Mean diaphyseal shortening was 3.9 ㎜ at skeletal maturity, but this increased to 5.8 ㎜ when only patients with severe shortening (20 ㎜ or more) were included. Conclusion: Our findings suggest that diaphyseal shortening is likely to be minimized by the implementation of limb exercise programs.

Comparison between braced and non-braced Legg–Calvé–Perthes-disease patients: a radiological outcome study

Twenty-three hips of 23 Legg–Calvé–Perthes-disease (LCPD) patients treated with abduction orthosis and 28 hips of 25 non-braced LCPD patients were evaluated radiologically retrospectively. The mean age of the brace group was 6.82 years and the mean follow-up was 12.30 years. The mean age and mean follow-up were 7.03 and 17.85 years for non-braced patients, respectively. The hips were evaluated according to lateral pillar classification. There were eight Herring A, 15 Herring B and five Herring C hips in the non-braced patients group; and there were five Herring A, 11 Herring-B and seven Herring C hips in the brace group. The groups were similar in terms of mean age, mean follow-up, sex distribution and lateral pillar grade. Patients' end results were evaluated according to Stulberg classification. All Herring A patients healed with Stulberg class 1 or 2, either braced or non-braced. Fifty-three percent of non-braced hips and 65% of the hips treated with brace healed with satisfactory radiological outcome. There were no significant differences between the groups in terms of end result. The overall results of this study suggest that Herring's lateral pillar classification is a useful system for the prediction of the long-term outcome of the disease and that there was no significant difference between the braced and non-braced patients in terms of radiological end result.

The 1226g (N370S) Gaucher mutation among patients with Legg–Calve–Perthes disease

Legg–Calve–Perthes disease (LCPD) is an avascular necrosis of the femoral head with an annual incidence of 5–15/100,000. The estimated incidence of Gaucher disease, a lysosomal recessive storage disease, is 1:850, with a carrier rate of 1:17.5 for the 1226G (N370S) mutation among Ashkenazi Jews in whom there is a predilection. Since clinical and radiological findings of avascular hip necrosis due to either Gaucher disease or LCPD may be indistinguishable, misdiagnosis may occur. The purpose of this study was to evaluate the incidence of 1226G Gaucher mutation in a cohort of radiologically confirmed LCPD patients (diagnosed 1986–2000) in Israel. Enzyme assay was performed for confirmation of affected versus carrier status in patients with the 1226G mutation. In all, 78 LCPD patients, 86% males, 51% with severe bone disease, were studied. Family history was negative for Gaucher disease. Ethnic origin was 39% Ashkenazi Jewish, 6% Arab, and 55% other ethnicities. One Ashkenazi Jewish LCPD patient was homozygous for the 1226G mutation, and 4 LCPD patients were carriers: 3 Ashkenazi Jewish and 1 Arab patient. The frequency of the 1226G mutation among the LCPD patients was increased relative to historical Ashkenazi Jewish Israeli controls ( P = 0.01). Since Gaucher disease may be misdiagnosed as LCPD, glucocerebrosidase enzyme testing is recommended among Ashkenazi Jewish children diagnosed with LCPD.

Inherited Risk Factors for Thrombophilia Among Children with Legg-Calvé-Perthes Disease

An inherited tendency to hypercoagulability has been suggested as a cause of vascular thrombosis resulting in Legg-Calvé-Perthes disease (LCPD). Here we carried out an investigation of the most common inherited risk factors for hypercoagulability including the mutation in the factor V gene (factor V Leiden), the transition 20.210G-->A in the prothrombin gene, and also the homozygosity for the 677C-->T transition in the methylenetetrahydrofolate reductase gene (MTHFR). The investigation was carried out among 61 Brazilian children with LCPD, who were compared with 296 individuals from the general population. The prevalence of the factor V Leiden mutation was higher in LCPD patients than in the controls (4.9 vs. 0.7%; p = 0.03). However, no patient had the prothrombin gene variant, and no difference was found between patients and controls when homozygosity for MTHFR-T (3.2 vs. 2.6%: p = 0.64) was determined. These data suggest that in our population, the heterozygosity for factor V Leiden was the only inherited risk factor associated with the development of LCPD.